The use of nerve stimulation for treating and controlling a variety of medical, psychiatric, and neurological disorders has seen significant growth over the last several decades. In particular, stimulation of the vagus nerve (the tenth cranial nerve, and part of the parasympathetic nervous system) has been the subject of considerable research. The vagus nerve is composed of somatic and visceral afferents (inward conducting nerve fibers, which convey impulses toward the brain) and efferents (outward conducting nerve fibers, which convey impulses to an effector to regulate activity such as muscle contraction or glandular secretion).
The rate of the heart is restrained in part by parasympathetic activity from the right and left vagus nerves. Low vagal nerve activity is considered to be related to various arrhythmias, including tachycardia, ventricular accelerated rhythm, and rapid atrial fibrillation. By artificially stimulating the vagus nerves, it is possible to slow the heart, allowing the heart to more completely relax and the ventricles to experience increased filling. With larger diastolic volumes, the heart may beat more efficiently because it may expend less energy to overcome the myocardial viscosity and elastic forces of the heart with each beat.
Stimulation of the vagus nerve has been proposed as a method for treating various heart conditions, including heart failure and atrial fibrillation. Heart failure is a cardiac condition characterized by a deficiency in the ability of the heart to pump blood throughout the body and/or to prevent blood from backing up in the lungs. Customary treatment of heart failure includes medication and lifestyle changes. It is often desirable to lower the heart rates of subjects suffering from faster than normal heart rates. The effectiveness of beta blockers in treating heart disease is attributed in part to their heart-rate-lowering effect.
Bilgutay et al., in “Vagal tuning: a new concept in the treatment of supraventricular arrhythmias, angina pectoris, and heart failure,” J. Thoracic Cardiovas. Surg. 56(1):71-82, July, 1968, which is incorporated herein by reference, studied the use of a permanently-implanted device with electrodes to stimulate the right vagus nerve for treatment of supraventricular arrhythmias, angina pectoris, and heart failure. Experiments were conducted to determine amplitudes, frequencies, wave shapes and pulse lengths of the stimulating current to achieve slowing of the heart rate. The authors additionally studied an external device, triggered by the R-wave of the electrocardiogram (ECG) of the subject to provide stimulation only upon an achievement of a certain heart rate. They found that when a pulsatile current with a frequency of ten pulses per second and 0.2 milliseconds pulse duration was applied to the vagus nerve, the heart rate could be decreased to half the resting rate while still preserving sinus rhythm. Low amplitude vagal stimulation was employed to control induced tachycardias and ectopic beats. The authors further studied the use of the implanted device in conjunction with the administration of Isuprel, a sympathomimetic drug. They found that Isuprel retained its inotropic effect of increasing contractility, while its chronotropic effect was controlled by the vagal stimulation: “An increased end diastolic volume brought about by slowing of the heart rate by vagal tuning, coupled with increased contractility of the heart induced by the inotropic effect of Isuprel, appeared to increase the efficiency of cardiac performance” (p. 79).
US Patent Application Publications 2005/0197675 and 2005/0267542 to Ben-David, which are assigned to the assignee of the present application and is incorporated herein by reference, describe apparatus including an electrode device, adapted to be coupled to a site of a subject; and a control unit, adapted to drive the electrode device to apply a current to the site intermittently during alternating “on” and “off” periods, each of the “on” periods having an “on” duration equal to between 1 and 10 seconds, and each of the “off” periods having an “off” duration equal to at least 50% of the “on” duration. In some embodiments, the control unit is configured to gradually ramp the commencement and/or termination of stimulation. In order to achieve the gradual ramp, the control unit is typically configured to gradually modify one or more stimulation parameters, such as those described hereinabove, e.g., pulse amplitude, pulses per trigger (PPT), pulse frequency, pulse width, “on” time, and/or “off” time. As appropriate, one or more of these parameters are varied by less than 50% of a pre-termination value per heart beat, in order to achieve the gradual ramp. For example, stimulation at 5 PPT may be gradually terminated by reducing the PPT by 1 pulse per hour. Alternatively, one or more of the parameters are varied by less than 5% per heart beat, in order to achieve the gradual ramp.
U.S. Pat. No. 6,167,304 to Loos, which is incorporated herein by reference, describes techniques for manipulating the nervous system of a subject by applying to the skin a pulsing external electric field which, although too weak to cause classical nerve stimulation, modulates the normal spontaneous spiking patterns of certain kinds of afferent nerves. For certain pulse frequencies the electric field stimulation can excite in the nervous system resonances with observable physiological consequences. Pulse variability is introduced for the purpose of thwarting habituation of the nervous system to the repetitive stimulation, or to alleviate the need for precise tuning to a resonance frequency, or to control pathological oscillatory neural activities such as tremors or seizures. Pulse generators with stochastic and deterministic pulse variability are described, and the output of a generator of the latter type is characterized. Techniques for achieving pulse variability include ramping the pulse frequency in time, or switching the pulses on and off according to a certain schedule determined by dedicated digital circuitry or by a programmable microprocessor.
US Patent Application Publication 2005/0222644 to Killian et al., which is incorporated herein by reference, describes a method for stimulating nerve or tissue fibers and a prosthetic hearing device implementing same. The method comprises: generating a stimulation signal comprising a plurality of pulse bursts each comprising a plurality of pulses; and distributing said plurality of pulse bursts across one or more electrodes each operatively coupled to nerve or tissue fibers such that each of said plurality of pulse bursts delivers a charge to said nerve or tissue fibers to cause dispersed firing in said nerve or tissue fibers. In an embodiment, individual pulses of a pulse burst are non-repeatedly interleaved on three channels. Multiple pulses may be repeated on one channel.
U.S. Pat. No. 5,562,718 to Palermo, which is incorporated herein by reference, describes an electronic neuromuscular stimulation device that is operated by a control unit. The control unit includes at least two output channels to which are connected to a corresponding set of electrode output cables. Each cable has attached a positive electrode and a negative electrode that are attached to selected areas of a patient's anatomy. The control unit also includes controls, indicators, and circuitry that produce nerve stimulation pulses that are applied to the patient through the electrodes. The nerve stimulation pulses consist of individual pulses that are arranged into pulse trains and pulse train patterns. The pulse train patterns, whose selection depends on the type of ailment being treated, includes sequential patterns, delayed overlapping patterns, triple-phase overlapping patterns, reciprocal pulse trains, and delayed sequenced “sprint interval” patterns. The overlapping patterns are described as being particularly timed to take advantage of neurological enhancement. In an embodiment, the pulse trains operate at a pulse rate interval of between 10 and 20 milliseconds which corresponds to a frequency of between 50 Hz and 100 Hz respectively. If a ramp frequency is used, it is applied just prior to the application of a long pulse train. The ramp frequency varies between 18 and 50 Hz and progresses over a 0.5 to 2.0 second period.
U.S. Pat. No. 5,707,400 to Terry, Jr. et al., which is incorporated herein by reference, describes a method for treating patients suffering from refractory hypertension, which includes identifying a patient suffering from the disorder and applying a stimulating electrical signal to the patient's vagus nerve predetermined to modulate the electrical activity of the nerve and to alleviate the hypertension. The stimulating signal is a pulse waveform with programmable signal parameter values including pulse width, output current, frequency, on time and off time. Patient discomfort may be alleviated by a ramping up the pulses during the first two seconds of stimulation, rather than abrupt application at the programmed level.
U.S. Pat. No. 6,928,320 to King, which is incorporated herein by reference, describes techniques for producing a desired effect by therapeutically activating tissue at a first site within a patient's body, and reducing a corresponding undesired side effect by blocking activation of tissue or conduction of action potentials at a second site within the patient's body by applying high frequency stimulation and/or direct current pulses at or near the second site. Time-varying DC pulses may be used before or after a high frequency blocking signal. The high frequency stimulation may begin before and continue during the therapeutic activation. The high frequency stimulation may begin with a relatively low amplitude, and the amplitude may be gradually increased. The desired effect may be promotion of micturition or defecation and the undesired side effect may be sphincter contraction. The desired effect may be defibrillation of the patient's atria or defibrillation of the patient's ventricles, and the undesired side effect may be pain. In an embodiment, the amplitude of the pulse waveform is ramped up or gradually increased at the beginning of the waveform, and ramped down or gradually decreased at the end of the waveform, respectively. Such ramping may be used in order to minimize creation of any action potentials that may be caused by more abruptly starting and/or more abruptly stopping the high frequency blocking stimulation.
US Patent Application Publication 2006/0129205 to Boveja et al., which is incorporated herein by reference, describes techniques for providing rectangular and/or complex electrical pulses to cortical tissues of a patient for at least one of providing therapy or alleviating symptoms of neurological disorders including Parkinson's disease, or for providing improvement of functional recovery following stroke. The intracranial electrodes may be implanted epidurally, or subdurally on the pia mater of the cortical surface. In an embodiment, a microcontroller is configured to deliver a pulse train by “ramping up” of the pulse train. The purpose of the ramping-up is to avoid sudden changes in stimulation when the pulse train begins.
U.S. Pat. No. 6,895,280 to Meadows et al., which is incorporated herein by reference, describes a spinal cord stimulation (SCS) system that includes multiple electrodes, multiple, independently programmable, stimulation channels within an implantable pulse generator (IPG) which channels can provide concurrent, but unique stimulation fields, permitting virtual electrodes to be realized. If slow start/end is enabled, the stimulation intensity is ramped up gradually when the IPG is first turned ON. If slow start/end is enabled, the stimulation intensity may be ramped down gradually rather than abruptly turned off. In an embodiment, a pulse ramping control technique for providing a slow turn-on of the stimulation burst includes modulating pulse amplitude at the beginning of a stimulation burst, while maintaining the pulse width as wide as possible, e.g., as wide as the final pulse duration.
US Patent Application Publication 2006/0015153A1 to Gliner et al., which is incorporated herein by reference, describes techniques for enhancing or affecting neural stimulation efficiency and/or efficacy. In one embodiment, electromagnetic stimulation is applied to a patient's nervous system over a first time domain according to a first set of stimulation parameters, and over a second time domain according to a second set of stimulation parameters. The first and second time domains may be sequential, simultaneous, or nested. Stimulation parameters may vary in accordance with one or more types of duty cycle, amplitude, pulse repetition frequency, pulse width, spatiotemporal, and/or polarity variations. Stimulation may be applied at subthreshold, threshold, and/or suprathreshold levels in one or more periodic, aperiodic (e.g., chaotic), and/or pseudo-random manners. In some embodiments stimulation may comprise a burst pattern having an interburst frequency corresponding to an intrinsic brainwave frequency, and regular and/or varying intraburst stimulation parameters. In an embodiment, within a time interval under consideration (e.g., 250 milliseconds), an interpulse interval of 8 milliseconds may occur 5 times; an interpulse interval of 10 milliseconds may occur 8 times; an interpulse interval of 12 milliseconds may occur 6 times; an interpulse interval of 14 milliseconds may occur 2 times; and interpulse intervals of 16 milliseconds and 18 milliseconds may each occur once.
U.S. Pat. No. 5,330,507 to Schwartz, which is incorporated herein by reference, describes techniques for stimulating the right or left vagus nerve with continuous and/or phasic electrical pulses, the latter in a specific relationship with the R-wave of the patient's electrogram. The automatic detection of the need for vagal stimulation is responsive to increases in the heart rate greater than a predetermined threshold, the occurrence of frequent or complex ventricular arrhythmias, and/or a change in the ST segment elevation greater than a predetermined or programmed threshold.
US Patent Application Publication 2003/0040774 to Terry et al., which is incorporated herein by reference, describes a device for treating patients suffering from congestive heart failure that includes an implantable neurostimulator for stimulating the patient's vagus nerve at or above the cardiac branch with an electrical pulse waveform at a stimulating rate sufficient to maintain the patient's heart beat at a rate well below the patient's normal resting heart rate, thereby allowing rest and recovery of the heart muscle, to increase in coronary blood flow, and/or growth of coronary capillaries. A metabolic need sensor detects the patient's current physical state and concomitantly supplies a control signal to the neurostimulator to vary the stimulating rate. If the detection indicates a state of rest, the neurostimulator rate reduces the patient's heart rate below the patient's normal resting rate. If the detection indicates physical exertion, the neurostimulator rate increases the patient's heart rate above the normal resting rate.
U.S. Pat. No. 5,203,326 to Collins, which is incorporated herein by reference, describes an antiarrhythmia pacemaker which detects a cardiac abnormality and responds with electrical stimulation of the heart combined with vagus nerve stimulation. The pacemaker controls electrical stimulation of the heart in terms of timing, frequency, amplitude, duration and other operational parameters, to provide such pacing therapies as antitachycardia pacing, cardioversion, and defibrillation. The vagal stimulation frequency is progressively increased in one-minute intervals, and, for the pulse delivery rate selected, the heart rate is described as being slowed to a desired, stable level by increasing the pulse current.
The following patent and patent application publications, all of which are incorporated herein by reference, may be of interest:    U.S. Pat. No. 6,473,644 to Terry, Jr. et al.    US Patent Publication 2003/0045909 to Gross et al.    U.S. Pat. No. 5,188,104 to Wernicke et al.    U.S. Pat. Nos. 6,272,377 and 6,400,982 to Sweeney et al.    U.S. Pat. Nos. 5,411,531 and 5,507,784 to Hill et al.    U.S. Pat. No. 6,628,987 to Hill et al.    U.S. Pat. No. 6,449,507 to Hill et al.    U.S. Pat. No. 6,542,774 to Hill et al.    US Patent Application 2003/0216775 to Hill et al.    US Patent Application 2002/0035335 to Schauerte    U.S. Pat. Nos. 6,240,314 and 6,493,585 to Plicchi et al.    U.S. Pat. No. 6,381,499 to Taylor et al.    U.S. Pat. No. 6,564,096 to Mest
The effect of vagal stimulation on heart rate and other aspects of heart function, including the relationship between the timing of vagal stimulation within the cardiac cycle and the induced effect on heart rate, has been studied in animals. For example, Zhang Y et al., in “Optimal ventricular rate slowing during atrial fibrillation by feedback AV nodal-selective vagal stimulation,” Am J Physiol Heart Circ Physiol 282:H1102-H1110 (2002), describe the application of selective vagal stimulation by varying the nerve stimulation intensity, in order to achieve graded slowing of heart rate. This article is incorporated herein by reference.
The following articles and book, which are incorporated herein by reference, may be of interest:    Levy M N et al., in “Parasympathetic Control of the Heart,” Nervous Control of Vascular Function, Randall W C ed., Oxford University Press (1984)    Levy M N et al. ed., Vagal Control of the Heart: Experimental Basis and Clinical Implications (The Bakken Research Center Series Volume 7), Futura Publishing Company, Inc., Armonk, N.Y. (1993)    Randall W C ed., Neural Regulation of the Heart, Oxford University Press (1977), particularly pages 100-106.    Armour J A et al. eds., Neurocardiology, Oxford University Press (1994)    Perez M G et al., “Effect of stimulating non-myelinated vagal axon on atrioventricular conduction and left ventricular function in anaesthetized rabbits,” Auton Neurosco 86 (2001)    Jones, J F X et al., “Heart rate responses to selective stimulation of cardiac vagal C fibres in anaesthetized cats, rats and rabbits,” J Physiol 489 (Pt 1):203-14 (1995)    Wallick D W et al., “Effects of ouabain and vagal stimulation on heart rate in the dog,” Cardiovasc. Res., 18(2):75-9 (1984)    Martin P J et al., “Phasic effects of repetitive vagal stimulation on atrial contraction,” Circ. Res. 52(6):657-63 (1983)    Wallick D W et al., “Effects of repetitive bursts of vagal activity on atrioventricular junctional rate in dogs,” Am J Physiol 237(3):H275-81 (1979)    Wallick D W et al., “Selective AV nodal vagal stimulation improves hemodynamics during acute atrial fibrillation in dogs,” Am J Physiol Heart Circ Physiol 281: H1490-H1497 (2001)    Fuster V and Ryden L E et al., “ACC/AHA/ESC Practice Guidelines—Executive Summary,” J Am Coll Cardiol 38(4):1231-65 (2001)    Fuster V and Ryden L E et al., “ACC/AHA/ESC Practice Guidelines—Full Text,” J Am Coll Cardiol 38(4):1266i-12661xx (2001)    Morady F et al., “Effects of resting vagal tone on accessory atrioventricular connections,” Circulation 81(1):86-90 (1990)    Waninger M S et al., “Electrophysiological control of ventricular rate during atrial fibrillation,” PACE 23:1239-1244 (2000)    Wijffels M C et al., “Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation,” Circulation 96(10):3710-20 (1997)    Wijffels M C et al., “Atrial fibrillation begets atrial fibrillation,” Circulation 92:1954-1968 (1995)    Goldberger A L et al., “Vagally-mediated atrial fibrillation in dogs: conversion with bretylium tosylate,” Int J Cardiol 13(1):47-55 (1986)    Takei M et al., “Vagal stimulation prior to atrial rapid pacing protects the atrium from electrical remodeling in anesthetized dogs,” Jpn Circ J 65(12):1077-81 (2001)    Friedrichs G S, “Experimental models of atrial fibrillation/flutter,” J Pharmacological and Toxicological Methods 43:117-123 (2000)    Hayashi H et al., “Different effects of class Ic and III antiarrhythmic drugs on vagotonic atrial fibrillation in the canine heart,” Journal of Cardiovascular Pharmacology 31:101-107 (1998)    Morillo C A et al., “Chronic rapid atrial pacing. Structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation,” Circulation 91:1588-1595 (1995)    Lew S J et al., “Stroke prevention in elderly patients with atrial fibrillation,” Singapore Med J 43(4):198-201 (2002)    Higgins C B, “Parasympathetic control of the heart,” Pharmacol. Rev. 25:120-155 (1973)    Hunt R, “Experiments on the relations of the inhibitory to the accelerator nerves of the heart,” J. Exptl. Med. 2:151-179 (1897)    Billette J et al., “Roles of the AV junction in determining the ventricular response to atrial fibrillation,” Can J Physiol Pharamacol 53(4)575-85 (1975)    Stramba-Badiale M et al., “Sympathetic-Parasympathetic Interaction and Accentuated Antagonism in Conscious Dogs,” American Journal of Physiology 260 (2Pt 2):H335-340 (1991)    Garrigue S et al., “Post-ganglionic vagal stimulation of the atrioventricular node reduces ventricular rate during atrial fibrillation,” PACE 21(4), 878 (Part II) (1998)    Kwan H et al., “Cardiovascular adverse drug reactions during initiation of antiarrhythmic therapy for atrial fibrillation,” Can J Hosp Pharm 54:10-14 (2001)    Jidéus L, “Atrial fibrillation after coronary artery bypass surgery: A study of causes and risk factors,” Acta Universitatis Upsaliensis, Uppsala, Sweden (2001)    Borovikova L V et al., “Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin,” Nature 405(6785):458-62 (2000)    Wang H et al., “Nicotinic acetylcholine receptor alpha-7 subunit is an essential regulator of inflammation,” Nature 421:384-388 (2003)    Vanoli E et al., “Vagal stimulation and prevention of sudden death in conscious dogs with a healed myocardial infarction,” Circ Res 68(5):1471-81 (1991)    De Ferrari G M, “Vagal reflexes and survival during acute myocardial ischemia in conscious dogs with healed myocardial infarction,” Am J Physiol 261(1 Pt 2):H63-9 (1991)    Li D et al., “Promotion of Atrial Fibrillation by Heart Failure in Dogs: Atrial Remodeling of a Different Sort,” Circulation 100(1):87-95 (1999)    Feliciano L et al., “Vagal nerve stimulation during muscarinic and beta-adrenergic blockade causes significant coronary artery dilation,” Cardiovasc Res 40(1):45-55 (1998)    Carlson M D et al., “Selective stimulation of parasympathetic nerve fibers to the human sinoatrial node,” Circulation 85:1311-1317 (1992)    Pagé P L et al., “Regional distribution of atrial electrical changes induced by stimulation of extracardiac and intracardiac neural elements,” J Thorac Cardiovasc Surg 109(2):377-88 (1995)    Masato Tsuboi et al., “Inotropic, chronotropic, and dromotropic effects mediated via parasympathetic ganglia in the dog heart,” Am J Physiol Heart Circ Physiol 279: H1201-H1207 (2000)    Furukawa Y et al., “Differential blocking effects of atropine and gallamine on negative chronotropic and dromotropic responses to vagus stimulation in anesthetized dogs,” J Pharmacol Exp Ther 251(3):797-802 (1989)    Bluemel K M, “Parasympathetic postganglionic pathways to the sinoatrial node,” J Physiol 259(5 Pt 2):H1504-10 (1990)    Mazgalev T N, “AV Nodal Physiology,” Heart Rhythm Society (www.hrsonline.org) (no date)    Bibevski S et al., “Ganglionic Mechanisms Contribute to Diminished Vagal Control in Heart Failure,” Circulation 99:2958-2963 (1999)    Hirose M et al., “Pituitary Adenylate Cyclase-Activating Polypeptide-27 Causes a Biphasic Chronotropic Effect and Atrial Fibrillation in Autonomically Decentralized, Anesthetized Dogs,” J Pharmacol Exp Ther 283(2):478-87 (1997)    Chen S A et al., “Intracardiac stimulation of human parasympathetic nerve fibers induces negative dromotropic effects: implication with the lesions of radiofrequency catheter ablation,” J Cardiovasc Electrophysiol 9(3):245-52 (1998)    Cooper et al., “Neural effects on sinus rate and atrial ventricular conduction produced by electrical stimulation from a transvenous electrode catheter in the canine right pulmonary artery” Circ Res Vol. 46(1):48-57 (1980)    Kamath et al., “Effect of vagal nerve electrostimulation on the power spectrum of heart rate variability in man,” Pacing Clin Electrophysiol 15:235-43 (1992)    Kleiger R E et al., “Decreased heart rate variability and its association with increased mortality after myocardial infarction,” Am J Cardiol 59: 256-262 (1987)    Akselrod S et al., “Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control,” Science 213: 220-222 (1981)
A number of patents describe techniques for treating arrhythmias and/or ischemia by, at least in part, stimulating the vagus nerve. Arrhythmias in which the heart rate is too fast include fibrillation, flutter and tachycardia. Arrhythmia in which the heart rate is too slow is known as bradyarrhythmia. U.S. Pat. No. 5,700,282 to Zabara, which is incorporated herein by reference, describes techniques for stabilizing the heart rhythm of a patient by detecting arrhythmias and then electronically stimulating the vagus and cardiac sympathetic nerves of the patient. The stimulation of vagus efferents directly causes the heart rate to slow down, while the stimulation of cardiac sympathetic nerve efferents causes the heart rate to quicken.
The following patent and patent application publications, all of which are incorporated herein by reference, may be of interest:    U.S. Pat. No. 5,330,507 to Schwartz    European Patent Application EP 0 688 577 to Holmström et al.    U.S. Pat. Nos. 5,690,681 and 5,916,239 to Geddes et al.    US Patent Publication 2003/0229380 to Adams et al.    U.S. Pat. No. 6,511,500 to Rahme    U.S. Pat. No. 5,199,428 to Obel et al.    U.S. Pat. Nos. 5,334,221 to Bardy and 5,356,425 to Bardy et al.    U.S. Pat. No. 5,522,854 to Ideker et al.    U.S. Pat. No. 6,434,424 to Igel et al.    US Patent Application Publication 2002/0120304 to Mest    U.S. Pat. Nos. 6,006,134 and 6,266,564 to Hill et al.    PCT Publication WO 02/085448 to Foreman et al.    U.S. Pat. No. 5,243,980 to Mehra    U.S. Pat. No. 5,658,318 to Stroetmann et al.    U.S. Pat. No. 6,292,695 to Webster, Jr. et al.    U.S. Pat. No. 6,134,470 to Hartlaub
A number of patents and articles describe other methods and devices for stimulating nerves to achieve a desired effect. Often these techniques include a design for an electrode or electrode cuff.
The following patent and patent application publications, all of which are incorporated herein by reference, may be of interest:    US Patent Publication 2003/0050677 to Gross et al.    U.S. Pat. No. 4,608,985 to Crish et al.    U.S. Pat. No. 4,649,936 to Ungar et al.    PCT Patent Publication WO 01/10375 to Felsen et al.    U.S. Pat. No. 5,755,750 to Petruska et al.    U.S. Pat. No. 6,600,956 to Maschino et al.
The following articles, which are incorporated herein by reference, may be of interest:    Ungar I J et al., “Generation of unidirectionally propagating action potentials using a monopolar electrode cuff,” Annals of Biomedical Engineering, 14:437-450 (1986)    Sweeney J D et al., “An asymmetric two electrode cuff for generation of unidirectionally propagated action potentials,” IEEE Transactions on Biomedical Engineering, vol. BME-33(6) (1986)    Sweeney J D et al., “A nerve cuff technique for selective excitation of peripheral nerve trunk regions,” IEEE Transactions on Biomedical Engineering, 37(7) (1990)    Naples G G et al., “A spiral nerve cuff electrode for peripheral nerve stimulation,” by IEEE Transactions on Biomedical Engineering, 35(11) (1988)    van den Honert C et al., “Generation of unidirectionally propagated action potentials in a peripheral nerve by brief stimuli,” Science, 206:1311-1312 (1979)    van den Honert C et al., “A technique for collision block of peripheral nerve: Single stimulus analysis,” MP-11, IEEE Trans. Biomed. Eng. 28:373-378 (1981)    van den Honert C et al., “A technique for collision block of peripheral nerve: Frequency dependence,” MP-12, IEEE Trans. Biomed. Eng. 28:379-382 (1981)    Rijkhoff N J et al., “Acute animal studies on the use of anodal block to reduce urethral resistance in sacral root stimulation,” IEEE Transactions on Rehabilitation Engineering, 2(2):92 (1994)    Mushahwar V K et al., “Muscle recruitment through electrical stimulation of the lumbo-sacral spinal cord,” IEEE Trans Rehabil Eng, 8(1):22-9 (2000)    Deurloo K E et al., “Transverse tripolar stimulation of peripheral nerve: a modelling study of spatial selectivity,” Med Biol Eng Comput, 36(1):66-74 (1998)    Tarver W B et al., “Clinical experience with a helical bipolar stimulating lead,” Pace, Vol. 15, October, Part II (1992)    Manfredi M, “Differential block of conduction of larger fibers in peripheral nerve by direct current,” Arch. Ital. Biol., 108:52-71 (1970)
In physiological muscle contraction, nerve fibers are recruited in the order of increasing size, from smaller-diameter fibers to progressively larger-diameter fibers. In contrast, artificial electrical stimulation of nerves using standard techniques recruits fibers in a larger- to smaller-diameter order, because larger-diameter fibers have a lower excitation threshold. This unnatural recruitment order causes muscle fatigue and poor force gradation. Techniques have been explored to mimic the natural order of recruitment when performing artificial stimulation of nerves to stimulate muscles.
Fitzpatrick et al., in “A nerve cuff design for the selective activation and blocking of myelinated nerve fibers,” Ann. Conf. of the IEEE Eng. in Medicine and Biology Soc, 13(2), 906 (1991), which is incorporated herein by reference, describe a tripolar electrode used for muscle control. The electrode includes a central cathode flanked on its opposite sides by two anodes. The central cathode generates action potentials in the motor nerve fiber by cathodic stimulation. One of the anodes produces a complete anodal block in one direction so that the action potential produced by the cathode is unidirectional. The other anode produces a selective anodal block to permit passage of the action potential in the opposite direction through selected motor nerve fibers to produce the desired muscle stimulation or suppression.
The following articles, patent publications, and patent application publications, all of which are incorporated herein by reference, may be of interest:    Rijkhoff N J et al., “Orderly recruitment of motoneurons in an acute rabbit model,” Ann. Conf. of the IEEE Eng., Medicine and Biology Soc., 20(5):2564 (1998)    Rijkhoff N J et al., “Selective stimulation of small diameter nerve fibers in a mixed bundle,” Proceedings of the Annual Project Meeting Sensations/Neuros and Mid-Term Review Meeting on the TMR-Network Neuros, Apr. 21-23, 1999, pp. 20-21 (1999)    Baratta R et al., “Orderly stimulation of skeletal muscle motor units with tripolar nerve cuff electrode,” IEEE Transactions on Biomedical Engineering, 36(8):836-43 (1989)    Levy M N, Blattberg B., “Effect of vagal stimulation on the overflow of norepinephrine into the coronary sinus during sympathetic nerve stimulation in the dog,” Circ Res 1976 February; 38(2):81-4    Lavallee et al. “Muscarinic inhibition of endogenous myocardial catecholamine liberation in the dog,” Can J Physiol Pharmacol 1978 August; 56(4):642-9    Mann D L, Kent R L, Parsons B, Cooper G, “Adrenergic effects on the biology of the adult mammalian cardiocyte,” Circulation 1992 February; 85(2):790-804    Mann D L, “Basic mechanisms of disease progression in the failing heart: role of excessive adrenergic drive,” Prog Cardiovasc Dis 1998 July-August; 41(1 suppl 1):1-8    Barzilai A, Daily D, Zilkha-Falb R, Ziv I, Offen D, Melamed E, Sirv A, “The molecular mechanisms of dopamine toxicity,” Adv Neurol 2003; 91:73-82
The following articles, which are incorporated herein by reference, describe techniques using point electrodes to selectively excite peripheral nerve fibers:    Grill W M et al., “Inversion of the current-distance relationship by transient depolarization,” IEEE Trans Biomed Eng, 44(1):1-9 (1997)    Goodall E V et al., “Position-selective activation of peripheral nerve fibers with a cuff electrode,” IEEE Trans Biomed Eng, 43(8):851-6 (1996)    Veraart C et al., “Selective control of muscle activation with a multipolar nerve cuff electrode,” IEEE Trans Biomed Eng, 40(7):640-53 (1993)    U.S. Pat. No. 6,620,186 to Saphon et al.    U.S. Pat. No. 6,393,323 to Sawan et al.    U.S. Pat. No. 5,891,179 to Er et al.    U.S. Pat. No. 6,366,813 to DiLorenzo    US Patent Application Publication 2004/0172075 to Shafer et al.    U.S. Pat. No. 6,341,236 to Osorio et al.